Arrestin-like proteins mediate ubiquitination and endocytosis of the yeast metal transporter Smf1.
Many plasma membrane proteins in yeast are ubiquitinated and endocytosed, but how they are recognized for modification has remained unknown. Here, we show that the manganese transporter Smf1 is endocytosed when cells are exposed to cadmium ions, that this endocytosis depends on Rsp5-dependent ubiquitination of specific lysines and that it also requires phosphorylation at nearby sites. This phosphorylation is, however, constitutive rather than stress-induced. Efficient ubiquitination requires Ecm21 or Csr2, two members of a family of arrestin-like yeast proteins that contain several PY motifs and bind to Rsp5. Ecm21 also binds to phosphorylated Smf1, providing a link between Rsp5 and its substrate. PY motif-containing arrestin-like proteins are found in many species, including humans, and might have a general role as ubiquitin ligase adaptors.
Nikko
Elina
E
MRC Laboratory of Molecular Biology, Hills Road, Cambridge CB2 0QH, UK.
Sullivan
James A
JA
Pelham
Hugh R B
HR
D019393:Arrestin / Q000378:metabolism*; D002104:Cadmium / Q000633:toxicity; D027682:Cation Transport Proteins / Q000378:metabolism*; D003432:Cross-Linking Reagents; D004705:Endocytosis; D056827:Endosomal Sorting Complexes Required for Transport; D049452:Green Fluorescent Proteins; D008239:Lysine; D010766:Phosphorylation; D011485:Protein Binding; D011993:Recombinant Fusion Proteins; D012441:Saccharomyces cerevisiae / Q000166:cytology* / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*; D043743:Ubiquitin-Protein Ligase Complexes; D054875:Ubiquitination
D019393:Arrestin; D027682:Cation Transport Proteins; D003432:Cross-Linking Reagents; C516567:Ecm21 protein, S cerevisiae; D056827:Endosomal Sorting Complexes Required for Transport; D011993:Recombinant Fusion Proteins; C105116:SMF1 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D002104:Cadmium; D049452:Green Fluorescent Proteins; D043743:Ubiquitin-Protein Ligase Complexes; C469287:RSP5 protein, S cerevisiae; D008239:Lysine